The following discussion of the prior art is intended to present the invention in an appropriate technical context and allow its significance to be properly appreciated. Unless clearly indicated to the contrary, however, reference to any prior art in this specification should be construed as an admission that such art is widely known or forms part of common general knowledge in the field.
Venlafaxine, (±)-1-[2-(Dimethylamino)-1-(4-ethyoxyphenyl)ethyl]cyclohexanol is the first of a class of anti-depressants. Venlafaxine acts by inhibiting re-uptake of norepinephrine and serotonin, and is an alternative to the tricylic anti-depressants and selective re-uptake inhibitors. Venlafaxine has the following structure of formula (II).

O-desmethyl-venlafaxine, 4-[2-(dimethylamino)-1-(1-hydroxycylcohexyl)ethyl]phenol, is a major metabolite of venlafaxine (Effexor) and has been shown to inhibit norepinephrine and serotonin uptake. See Klarnerus, K. J. et al., “Introduction of the composite parameter to the pharmacokinetics of venlafaxine and its active O-desmethyl metabolite,” J. Clin. Pharmacol. 32:716-724 (1992). O-desmethyl-venlafaxine is also being targeted as the first non-hormonal based treatment for menopause represented by the following formula (I) is an active ingredient marketed under the proprietary name PRISTIQ®.

U.S. Pat. No. 4,535,186 discloses the process for the preparation of O-desmethyl-venlafaxine, which is shown in below mentioned scheme:

U.S. Pat. No. 5,043,466 discloses an improved process for preparing O-desmethyl-venlafaxine. U.S. Pat. No. 6,673,838 B2 (the U.S. Pat. No. '838 B2) discloses four crystalline forms and an amorphous form of O-desmethyl-venlafaxine succinate and processes for their preparation. In particular, the U.S. Pat. No. '838 B2 discloses two crystalline monohydrate forms designated as Form I and Form II, respectively; one crystalline hydrated form designated as Form III with a water content between hemihydrate and monohydrate; one crystalline anhydrous form designated as Form IV and an amorphous form of O-desmethyl-venlafaxine succinate.
U.S. Pat. No. 6,197,828 B2 discloses O-desmethyl-venlafaxine succinate in substantially pure form. U.S. Patent Application No. 2004/0180952 A1 discloses the process for preparation of O-desmethyl-venlafaxine by demethylation of venlafaxine with lithium diphenylphosphide.
Several processes for the preparation of O-desmethyl-venlafaxine have been disclosed, for example like U.S. Patent Application Nos. 2004/0158901 A1, 2007/0149813 A1, 2007/0299283 A1, 2008/0015259 A1, 2009/0246284 A1 and U.S. Pat. No. 7,179,944 B2.
International (PCT) Publication WO 2008/013995 A1 discloses process for the preparation O-desmethyl-venlafaxine succinate which is incorporated herein as a reference in its entirety.
Several crystalline forms of O-desmethylvenlafaxine succinate and their processes for preparation have been disclosed, for example like U.S. Pat. No. 7,820,716 B2, U.S. Patent Application No. 2011/0184067 A1, International (PCT) Publication Nos. WO 2008/017886 A1, WO 2008/047167 A1, WO 2008/110338A1, WO 2008/156748 A2, WO 2009/009665 A2, WO 2009/010990 A2, WO 2009/027766 A1 and WO 2009/118758 A2.
U.S. Pat. No. 7,674,935 B2 discloses crytalline Form-A, Form-C and Form-D of O-desmethyl-venlafaxine base.
Polymorphism is the occurrence of different crystalline forms of a single compound and it is a property of some compounds and complexes. Thus, polymorphs are distinct solids sharing the same molecular formula, yet each polymorph may have distinct physical properties. Therefore, a single compound may give rise to a variety of polymorphic forms where each form has different and distinct physical properties, such as different solubility profiles, different melting point temperatures and/or different x-ray diffraction peaks. Since the solubility of each polymorph may vary, identifying the existence of pharmaceutical polymorphs is essential for providing pharmaceuticals with predicable solubility profiles. It is desirable to investigate all solid-state forms of a drug, including all polymorphic forms, and to determine the stability, dissolution and flow properties of each polymorphic form. The polymorphic forms of a compound can be distinguished in a laboratory by X-ray diffraction spectroscopy and by other methods such as, infrared spectrometry. For a general review of polymorphs and the pharmaceutical applications of polymorphs, See G. M. Wall, Pharm Manuf. 3, 33 (1986); J. K. Haleblian and W. McCrone, J. Pharm. Sci., 58, 911 (1969); and J. K. Haleblian, J. Pharm. Sci., 64, 1269 (1975), all of which are incorporated herein by reference.
The known crystalline forms of O-desmethyl-venlafaxine succinate are hydrates, which are very susceptible in presence of water. They are the hydrates like monohydrates, hemihydrates, anhydrous or even amorphous compounds. Therefore, the present invention provides new crystalline forms of O-desmethyl-venlafaxine succinate, which are stable and useful for pharmaceutical compositions that include the crystalline O-desmethyl-venlafaxine succinate.